Protein phosphatases in the RNAPII transcription cycle: erasers, sculptors, gatekeepers, and potential drug targets

Phosphoproteome and drug response effects mediated by the three Protein Phosphatase 2A inhibitor proteins CIP2A, SET and PME-1

(2020) Otto Kauko et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Localized Inhibition of Protein Phosphatase 1 by NUAK1 Promotes Spliceosome Activity and Reveals a MYC-Sensitive Feedback Control of Transcription

(2020) Giacomo Cossa et al.   MOLECULAR CELL

DAF-16/FOXO requires Protein Phosphatase 4 to initiate transcription of stress resistance and longevity promoting genes

(2020) Ilke Sen et al.   Nature Communications

Allosteric Activators of Protein Phosphatase 2A Display Broad Antitumor Activity Mediated by Dephosphorylation of MYBL2

(2020) Ken Morita et al.   CELL

Piecing Together a Broken Tumor Suppressor Phosphatase for Cancer Therapy

(2020) Jukka Westermarck et al.   CELL

Selective PP2A Enhancement through Biased Heterotrimer Stabilization

(2020) Daniel Leonard et al.   CELL

Structure and mechanism of the RNA polymerase II transcription machinery

(2020) Allison C. Schier et al.   GENES & DEVELOPMENT

RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

(2020) Jose F. Victorino et al.   PLoS Genetics

Nutrient-dependent control of RNA polymerase II elongation rate regulates specific gene expression programs by alternative polyadenylation

(2020) Carlo Yague-Sanz et al.   GENES & DEVELOPMENT

Dissecting the Pol II transcription cycle and derailing cancer with CDK inhibitors

(2020) Pabitra K. Parua et al.   Nature Chemical Biology

Transcriptional interference at tandem lncRNA and protein-coding genes: an emerging theme in regulation of cellular nutrient homeostasis

(2020) Stewart Shuman   NUCLEIC ACIDS RESEARCH

A unified view of the sequence and functional organization of the human RNA polymerase II promoter

(2020) Donal S Luse et al.   NUCLEIC ACIDS RESEARCH

Selective inhibition of CDK7 reveals high-confidence targets and new models for TFIIH function in transcription

(2020) Jenna K. Rimel et al.   GENES & DEVELOPMENT

Integrator Recruits Protein Phosphatase 2A to Prevent Pause Release and Facilitate Transcription Termination

(2020) Kai-Lieh Huang et al.   MOLECULAR CELL

A genetic screen for suppressors of hyper-repression of the fission yeast PHO regulon by Pol2 CTD mutation T4A implicates inositol 1-pyrophosphates as agonists of precocious lncRNA transcription termination

(2020) Angad Garg et al.   NUCLEIC ACIDS RESEARCH

Distinct Cdk9-phosphatase switches act at the beginning and end of elongation by RNA polymerase II

(2020) Pabitra K. Parua et al.   Nature Communications

Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase

(2020) Hai Zheng et al.   SCIENCE

WDR82/PNUTS-PP1 Prevents Transcription-Replication Conflicts by Promoting RNA Polymerase II Degradation on Chromatin

(2020) Helga B. Landsverk et al.   Cell Reports

How the cell cycle clock ticks

(2019) Mihkel Örd et al.   MOLECULAR BIOLOGY OF THE CELL

Promoter-proximal pausing of RNA polymerase II: a nexus of gene regulation

(2019) Leighton Core et al.   GENES & DEVELOPMENT

PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription

(2019) Nicole Steinbach et al.   NUCLEIC ACIDS RESEARCH

Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3′ processing and transcription termination

(2019) Ana M Sanchez et al.   NUCLEIC ACIDS RESEARCH

The Integrator complex cleaves nascent mRNAs to attenuate transcription

(2019) Deirdre C. Tatomer et al.   GENES & DEVELOPMENT

Pol II phosphorylation regulates a switch between transcriptional and splicing condensates

(2019) Yang Eric Guo et al.   NATURE

Organization and regulation of gene transcription

(2019) Patrick Cramer   NATURE

Tyr1 phosphorylation promotes phosphorylation of Ser2 on the C-terminal domain of eukaryotic RNA polymerase II by P-TEFb

(2019) Joshua E Mayfield et al.   eLife

Eukaryotic Transcription Turns 50

(2019) Patrick Cramer   CELL

A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes

(2019) Joshua D. Eaton et al.   GENES & DEVELOPMENT

The Integrator Complex Attenuates Promoter-Proximal Transcription at Protein-Coding Genes

(2019) Nathan D. Elrod et al.   MOLECULAR CELL

Control of RNA Pol II Speed by PNUTS-PP1 and Spt5 Dephosphorylation Facilitates Termination by a “Sitting Duck Torpedo” Mechanism

(2019) Michael A. Cortazar et al.   MOLECULAR CELL

Therapeutic targeting of PP2A

(2018) Caitlin M. O’Connor et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Emerging Roles of Non-Coding RNA Transcription

(2018) Minna U. Kaikkonen et al.   TRENDS IN BIOCHEMICAL SCIENCES

The Importance of Kinase–Phosphatase Integration: Lessons from Mitosis

(2018) Lendert Gelens et al.   TRENDS IN CELL BIOLOGY

Cdk9 regulates a promoter-proximal checkpoint to modulate RNA polymerase II elongation rate in fission yeast

(2018) Gregory T. Booth et al.   Nature Communications

Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics

(2018) Mónica Ferreira et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

PP1 Phosphatase Complexes: Undruggable No Longer

(2018) Paola Vagnarelli et al.   CELL

Target-Based Discovery of an Inhibitor of the Regulatory Phosphatase PPP1R15B

(2018) Agnieszka Krzyzosiak et al.   CELL

Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models

(2018) Waleed Minzel et al.   CELL

A substrate-trapping strategy for protein phosphatase PP1 holoenzymes using hypoactive subunit fusions

(2018) Dan Wu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A Cdk9–PP1 switch regulates the elongation–termination transition of RNA polymerase II

(2018) Pabitra K. Parua et al.   NATURE

Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II

(2018) Huasong Lu et al.   NATURE

Structure of paused transcription complex Pol II–DSIF–NELF

(2018) Seychelle M. Vos et al.   NATURE

Structure of activated transcription complex Pol II–DSIF–PAF–SPT6

(2018) Seychelle M. Vos et al.   NATURE

RNA polymerase II clustering through carboxy-terminal domain phase separation

(2018) Marc Boehning et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability

(2018) Dharmendra Dingar et al.   Nature Communications

The split protein phosphatase system

(2018) Anne Bertolotti   BIOCHEMICAL JOURNAL

RNA polymerase II CTD interactome with 3′ processing and termination factors in fission yeast and its impact on phosphate homeostasis

(2018) Ana M. Sanchez et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Elongation/Termination Factor Exchange Mediated by PP1 Phosphatase Orchestrates Transcription Termination

(2018) Tea Kecman et al.   Cell Reports

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

(2017) Jaya Sangodkar et al.   JOURNAL OF CLINICAL INVESTIGATION

Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation

(2017) Ameet Shetty et al.   MOLECULAR CELL

Genomics and evolution of protein phosphatases

(2017) Mark J. Chen et al.   Science Signaling

Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors

(2017) Sampada Kalan et al.   Cell Reports

An Asymmetrically Balanced Organization of Kinases versus Phosphatases across Eukaryotes Determines Their Distinct Impacts

(2017) Ilan Smoly et al.   PLoS Computational Biology

Genomics and evolution of protein phosphatases

(2017) Mark J. Chen et al.   Science Signaling

Dephosphorylating eukaryotic RNA polymerase II

(2016) Joshua E. Mayfield et al.   BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

CDK Substrate Phosphorylation and Ordering the Cell Cycle

(2016) Matthew P. Swaffer et al.   CELL

P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates

(2016) Miriam Sansó et al.   GENES & DEVELOPMENT

Divergence of a conserved elongation factor and transcription regulation in budding and fission yeast

(2016) Gregory T. Booth et al.   GENOME RESEARCH

Structure ofSaccharomyces cerevisiaeRtr1 reveals an active site for an atypical phosphatase

(2016) Seema Irani et al.   Science Signaling

Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics

(2016) Zachary C. Poss et al.   Cell Reports

Structural and Functional Analysis of the Cdk13/Cyclin K Complex

(2016) Ann Katrin Greifenberg et al.   Cell Reports

Structure ofSaccharomyces cerevisiaeRtr1 reveals an active site for an atypical phosphatase

(2016) Seema Irani et al.   Science Signaling

CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer

(2015) Yubao Wang et al.   CELL

All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase

(2015) Jaya Sangodkar et al.   FEBS Journal

Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

(2015) Liv M.I. Austenaa et al.   MOLECULAR CELL

Genetic and structural analysis of the essential fission yeast RNA polymerase II CTD phosphatase Fcp1

(2015) Beate Schwer et al.   RNA

FDA-approved small-molecule kinase inhibitors

(2015) Peng Wu et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor

(2014) Camilla L. Christensen et al.   CANCER CELL

CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer

(2014) Edmond Chipumuro et al.   CELL

Rtr1 Is a Dual Specificity Phosphatase That Dephosphorylates Tyr1 and Ser5 on the RNA Polymerase II CTD

(2014) Peter L. Hsu et al.   JOURNAL OF MOLECULAR BIOLOGY

Function and Control of RNA Polymerase II C-Terminal Domain Phosphorylation in Vertebrate Transcription and RNA Processing

(2014) J.-P. Hsin et al.   MOLECULAR AND CELLULAR BIOLOGY

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

(2014) Nicholas Kwiatkowski et al.   NATURE

A PP1–PP2A phosphatase relay controls mitotic progression

(2014) Agnes Grallert et al.   NATURE

RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation

(2014) Zuyao Ni et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

RNA polymerase II termination involves C-terminal-domain tyrosine dephosphorylation by CPF subunit Glc7

(2014) Amelie Schreieck et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

PhosphoSitePlus, 2014: mutations, PTMs and recalibrations

(2014) Peter V. Hornbeck et al.   NUCLEIC ACIDS RESEARCH

C-terminal domain small phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation

(2014) Edmund Nesti et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The structure and substrate specificity of human Cdk12/Cyclin K

(2014) Christian A. Bösken et al.   Nature Communications

CPF-Associated Phosphatase Activity Opposes Condensin-Mediated Chromosome Condensation

(2014) Vincent Vanoosthuyse et al.   PLoS Genetics

Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells

(2014) Nicolas Descostes et al.   eLife

Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons

(2014) Iris Jonkers et al.   eLife

Cyclin-dependent kinases

(2014) Marcos Malumbres   GENOME BIOLOGY

Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits

(2013) Yuanchao Xue et al.   CELL

Protein phosphatase 4 is phosphorylated and inactivated by Cdk in response to spindle toxins and interacts with γ-tubulin

(2013) Martin Voss et al.   CELL CYCLE

Evolution and functional cross-talk of protein post-translational modifications

(2013) Pedro Beltrao et al.   Molecular Systems Biology

A common structural scaffold in CTD phosphatases that supports distinct catalytic mechanisms

(2013) Tirso Pons et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

PNUTS/PP1 Regulates RNAPII-Mediated Gene Expression and Is Necessary for Developmental Growth

(2013) Anita Ciurciu et al.   PLoS Genetics

The PP1 binding code: a molecular-lego strategy that governs specificity

(2012) Ewald Heroes et al.   FEBS Journal

The RNA polymerase II CTD coordinates transcription and RNA processing

(2012) J.-P. Hsin et al.   GENES & DEVELOPMENT

Ssu72 Phosphatase-dependent Erasure of Phospho-Ser7 Marks on the RNA Polymerase II C-terminal Domain Is Essential for Viability and Transcription Termination

(2012) David W. Zhang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Fcp1 Dephosphorylation of the RNA Polymerase II C-Terminal Domain Is Required for Efficient Transcription of Heat Shock Genes

(2012) N. J. Fuda et al.   MOLECULAR AND CELLULAR BIOLOGY

Separate Domains of Fission Yeast Cdk9 (P-TEFb) Are Required for Capping Enzyme Recruitment and Primed (Ser7-Phosphorylated) Rpb1 Carboxyl-Terminal Domain Substrate Recognition

(2012) C. V. St. Amour et al.   MOLECULAR AND CELLULAR BIOLOGY

mRNA Decapping Factors and the Exonuclease Xrn2 Function in Widespread Premature Termination of RNA Polymerase II Transcription

(2012) Kris Brannan et al.   MOLECULAR CELL

A Universal RNA Polymerase II CTD Cycle Is Orchestrated by Complex Interplays between Kinase, Phosphatase, and Isomerase Enzymes along Genes

(2012) Alain R. Bataille et al.   MOLECULAR CELL

Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans

(2012) Karen Adelman et al.   NATURE REVIEWS GENETICS

Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II

(2012) Stéphane Larochelle et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Gene Loops Enhance Transcriptional Directionality

(2012) S. M. Tan-Wong et al.   SCIENCE

The yeast regulator of transcription protein Rtr1 lacks an active site and phosphatase activity

(2012) Kehui Xiang et al.   Nature Communications

Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition

(2012) Nadine Czudnochowski et al.   Nature Communications

Deciphering the RNA Polymerase II CTD Code in Fission Yeast

(2011) Beate Schwer et al.   MOLECULAR CELL

Ser7 Phosphorylation of the CTD Recruits the RPAP2 Ser5 Phosphatase to snRNA Genes

(2011) Sylvain Egloff et al.   MOLECULAR CELL

The C-Terminal Domain of RNA Polymerase II Is Modified by Site-Specific Methylation

(2011) R. J. Sims et al.   SCIENCE

Gene-specific RNA polymerase II phosphorylation and the CTD code

(2010) Hyunmin Kim et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Chemical-genomic dissection of the CTD code

(2010) Joshua R Tietjen et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

CDK8 is a positive regulator of transcriptional elongation within the serum response network

(2010) Aaron J Donner et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Uniform transitions of the general RNA polymerase II transcription complex

(2010) Andreas Mayer et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

A Global Protein Kinase and Phosphatase Interaction Network in Yeast

(2010) A. Breitkreutz et al.   SCIENCE

Serine/Threonine Phosphatases: Mechanism through Structure

(2009) Yigong Shi   CELL

TFIIH-Associated Cdk7 Kinase Functions in Phosphorylation of C-Terminal Domain Ser7 Residues, Promoter-Proximal Pausing, and Termination by RNA Polymerase II

(2009) K. Glover-Cutter et al.   MOLECULAR AND CELLULAR BIOLOGY

Rtr1 Is a CTD Phosphatase that Regulates RNA Polymerase II during the Transition from Serine 5 to Serine 2 Phosphorylation

(2009) Amber L. Mosley et al.   MOLECULAR CELL

Progression through the RNA Polymerase II CTD Cycle

(2009) Stephen Buratowski   MOLECULAR CELL

From Promiscuity to Precision: Protein Phosphatases Get a Makeover

(2009) David M. Virshup et al.   MOLECULAR CELL

TFIIH and P-TEFb Coordinate Transcription with Capping Enzyme Recruitment at Specific Genes in Fission Yeast

(2009) Laia Viladevall et al.   MOLECULAR CELL

Displacement affinity chromatography of protein phosphatase one (PP1) complexes

(2008) Greg BG Moorhead et al.   BMC BIOCHEMISTRY

Rtr1 Is theSaccharomyces cerevisiaeHomolog of a Novel Family of RNA Polymerase II-Binding Proteins

(2008) Patrick A. Gibney et al.   EUKARYOTIC CELL

PP2B and PP1  cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling

(2008) R. Chen et al.   GENES & DEVELOPMENT

The Structure of Fcp1, an Essential RNA Polymerase II CTD Phosphatase

(2008) Agnidipta Ghosh et al.   MOLECULAR CELL

The Glc7 Phosphatase Subunit of the Cleavage and Polyadenylation Factor Is Essential for Transcription Termination on snoRNA Genes

(2008) Eduard Nedea et al.   MOLECULAR CELL

Cracking the RNA polymerase II CTD code

(2008) Sylvain Egloff et al.   TRENDS IN GENETICS